ADH2/YMR303C Summary Help

Standard Name ADH2 1
Systematic Name YMR303C
Alias ADR2
Feature Type ORF, Verified
Description Glucose-repressible alcohol dehydrogenase II; catalyzes the conversion of ethanol to acetaldehyde; involved in the production of certain carboxylate esters; regulated by ADR1 (2, 3, 4 and see Summary Paragraph)
Name Description Alcohol DeHydrogenase
Chromosomal Location
ChrXIII:874337 to 873291 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
Gbrowse
Genetic position: 216 cM
Gene Ontology Annotations All ADH2 GO evidence and references
  View Computational GO annotations for ADH2
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
High-throughput
Regulators 14 genes
Resources
Pathways
Classical genetics
null
unspecified
Large-scale survey
null
overexpression
Resources
44 total interaction(s) for 38 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 21
  • Protein-peptide: 2
  • Reconstituted Complex: 1
  • Two-hybrid: 1

Genetic Interactions
  • Negative Genetic: 6
  • Phenotypic Enhancement: 7
  • Phenotypic Suppression: 1
  • Positive Genetic: 5

Resources
Expression Summary
histogram
Resources
Length (a.a.) 348
Molecular Weight (Da) 36,732
Isoelectric Point (pI) 6.72
Localization
Phosphorylation PhosphoGRID | PhosphoPep Database
Structure
Homologs
sequence information
ChrXIII:874337 to 873291 | ORF Map | GBrowse
Note: this feature is encoded on the Crick strand.
SGD ORF map
Genetic position: 216 cM
Last Update Coordinates: 2011-02-03 | Sequence: 1996-07-31
Subfeature details
Relative
Coordinates
Chromosomal
Coordinates
Most Recent Updates
Coordinates Sequence
CDS 1..1047 874337..873291 2011-02-03 1996-07-31
Retrieve sequences
Analyze Sequence
S288C only
S288C vs. other species
S288C vs. other strains
Resources
External Links All Associated Seq | E.C. | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000004918
SUMMARY PARAGRAPH for ADH2

In S. cerevisiae, there are five genes that encode alcohol dehydrogenases involved in ethanol metabolism, ADH1 to ADH5. Four of these enzymes, Adh1p, Adh3p, Adh4p, and Adh5p, reduce acetaldehyde to ethanol during glucose fermentation, while Adh2p catalyzes the reverse reaction of oxidizing ethanol to acetaldehyde (3, 5, 2, 6, 7).

The five ethanol dehydrogenases (Adh1p, Adh2p, Adh3p, Adh4p, and Adh5p) as well as the bifunctional enzyme Sfa1p are also involved in the production of fusel alcohols during fermentation (4). Fusel alcohols are end products of amino acid catabolism (of valine, leucine, isoleucine, methionine, phenylalanine, tryptophan, and tyrosine) via the Ehrlich pathway and contribute to the flavor and aroma of yeast-fermented foods and beverages (8). They may also have physiological roles. For example, exposing cells to isoamyl alcohol, derived from catabolism of leucine, stimulates filamentous growth (9, 10). Similarly, other fusel alcohols also stimulate filamentous growth in S. cerevisiae and biofilm formation in the pathogens Candida albicans and Candida dubliniensis (11, 12, reviewed in 8).

When glucose becomes depleted from the environment, Adh2p is responsible for catalyzing the initial step in the utilization of ethanol as a carbon source (13). S. cerevisiae cells lacking alcohol dehydrogenase activity are unable to grow when ethanol is the sole carbon source and these cells also accumulate high levels of glycerol (14). Although ADH1 and ADH2 share 89% sequence similarity, their gene products differ in metabolic directionality due to their differences in substrate affinity; Adh2p has a ten-fold lower Km for ethanol than all the other alcohol dehydrogenases (5, 15).

Two cis-acting elements in the ADH2 promoter, UAS1 (upstream activation site) and UAS2/CSRE (carbon-source responsive element), are both necessary for maximal ADH2 expression (13, 16). In the absence of a fermentable carbon source, these sites are bound cooperatively by the transcriptional activators Adr1p and Cat8p (16); Adr1p binds to the UAS1 site while Cat8p binds to the UAS2/CSRE site (13, 17, 18). The presence of glucose downregulates the levels of these transcription factors which in turn results in ADH2 expression being repressed by several hundred-fold (19, 20, 13).

About the medium-chain dehydrogenase/reductase (MDR) family

Medium-chain dehydrogenase/reductases (MDRs), sometimes referred to as long-chain dehydrogenases (21), constitute an ancient and widespread enzyme superfamily with members found in Bacteria, Archaea, and Eukaryota (22, 23). Many MDR members are basic metabolic enzymes acting on alcohols or aldehydes, and thus these enzymes may have roles in detoxifying alcohols and related compounds, protecting against environmental stresses such as osmotic shock, reduced or elevated temperatures, or oxidative stress (22). The family also includes the mammalian zeta-crystallin lens protein, which may protect the lens against oxidative damage and enzymes which produce lignocellulose in plants (22).

MDR enzymes typically have subunits of about 350 aa residues and are two-domain proteins, with a catalytic domain and a second domain for binding to the nicotinamide cofactor, either NAD(H) or NADP(H) (22, 23). They contain 0, 1, or 2 zinc atoms (24). When zinc is present, it is involved in catalysis at the active site.

Based on phylogenetic and sequence analysis, the members of the MDR superfamily can be further divided into more closely related subgroups (22, 23). In families which are widespread from prokaryotes to eukaryotes, some members appear conserved across all species, while others appear to be due to lineage specific duplications. Some subgroups are only found in certain taxa. S. cerevisiae contains fifteen (22) or twenty-one (23) members of the MDR superfamily, listed below. The difference in number is due to six sequences that were included as members of the quinone oxidoreductase family by Riveros-Rosas et al. (23) but not by Nordling et al. (22).

Zinc-containing enzyme groups:
- PDH; "polyol" dehydrogenase family - BDH1, BDH2, SOR1, SOR2, XYL2
- ADH; class III alcohol dehydrogenase family - SFA1
- Y-ADH; "yeast" alcohol dehydrogenase family - ADH1, ADH2, ADH3, ADH5
- CADH; cinnamyl alcohol dehydrogenase family - ADH6, ADH7

Non-zinc-containing enzyme groups:
- NRBP; nuclear receptor binding protein (23) or MRF; mitochondrial respiratory function (22) family - ETR1
- QOR; quinone oxidoreductase family - ZTA1 (22, 23), AST1, AST2, YCR102C, YLR460C, YMR152W, YNL134C (23)
- LTD; leukotriene B4 dehydrogenases - YML131W
- ER; enoyl reductases (23) or ACR; acyl-CoA reductase (22) family - no members in S. cerevisiae

Last updated: 2005-11-22 Contact SGD

References cited on this page View Complete Literature Guide for ADH2
1) Ciriacy, M.  (1985) Personal Communication, Mortimer Map Edition 9
2) Young ET and Pilgrim D  (1985) Isolation and DNA sequence of ADH3, a nuclear gene encoding the mitochondrial isozyme of alcohol dehydrogenase in Saccharomyces cerevisiae. Mol Cell Biol 5(11):3024-34
3) Bennetzen JL and Hall BD  (1982) The primary structure of the Saccharomyces cerevisiae gene for alcohol dehydrogenase. J Biol Chem 257(6):3018-25
4) Dickinson JR, et al.  (2003) The catabolism of amino acids to long chain and complex alcohols in Saccharomyces cerevisiae. J Biol Chem 278(10):8028-34
5) Russell DW, et al.  (1983) Nucleotide sequence of the yeast alcohol dehydrogenase II gene. J Biol Chem 258(4):2674-82
6) Drewke C and Ciriacy M  (1988) Overexpression, purification and properties of alcohol dehydrogenase IV from Saccharomyces cerevisiae. Biochim Biophys Acta 950(1):54-60
7) Smith MG, et al.  (2004) Microbial synergy via an ethanol-triggered pathway. Mol Cell Biol 24(9):3874-84
8) Hazelwood LA, et al.  (2008) The Ehrlich pathway for fusel alcohol production: a century of research on Saccharomyces cerevisiae metabolism. Appl Environ Microbiol 74(8):2259-66
9) Kern K, et al.  (2004) Isoamyl alcohol-induced morphological change in Saccharomyces cerevisiae involves increases in mitochondria and cell wall chitin content. FEMS Yeast Res 5(1):43-9
10) Hauser M, et al.  (2007) A transcriptome analysis of isoamyl alcohol-induced filamentation in yeast reveals a novel role for Gre2p as isovaleraldehyde reductase. FEMS Yeast Res 7(1):84-92
11) Dickinson JR  (1996) 'Fusel' alcohols induce hyphal-like extensions and pseudohyphal formation in yeasts. Microbiology 142 ( Pt 6)():1391-7
12) Lorenz MC, et al.  (2000) Characterization of alcohol-induced filamentous growth in Saccharomyces cerevisiae. Mol Biol Cell 11(1):183-99
13) Ciriacy M  (1975) Genetics of alcohol dehydrogenase in Saccharomyces cerevisiae. II. Two loci controlling synthesis of the glucose-repressible ADH II. Mol Gen Genet 138(2):157-64
14) Wills C and Phelps J  (1975) A technique for the isolation of yeast alcohol dehydrogenase mutants with altered substrate specificity. Arch Biochem Biophys 167(2):627-37
15) Wills C  (1976) Production of yeast alcohol dehydrogenase isoenzymes by selection. Nature 261(5555):26-9
16) Tachibana C, et al.  (2005) Combined global localization analysis and transcriptome data identify genes that are directly coregulated by Adr1 and Cat8. Mol Cell Biol 25(6):2138-46
17) Eisen A, et al.  (1988) The yeast regulatory protein ADR1 binds in a zinc-dependent manner to the upstream activating sequence of ADH2. Mol Cell Biol 8(10):4552-6
18) Walther K and Schuller HJ  (2001) Adr1 and Cat8 synergistically activate the glucose-regulated alcohol dehydrogenase gene ADH2 of the yeast Saccharomyces cerevisiae. Microbiology 147(Pt 8):2037-44
19) Blumberg H, et al.  (1988) Regulation of expression and activity of the yeast transcription factor ADR1. Mol Cell Biol 8(5):1868-76
20) Hedges D, et al.  (1995) CAT8, a new zinc cluster-encoding gene necessary for derepression of gluconeogenic enzymes in the yeast Saccharomyces cerevisiae. Mol Cell Biol 15(4):1915-22
21) Jornvall H, et al.  (1981) Alcohol and polyol dehydrogenases are both divided into two protein types, and structural properties cross-relate the different enzyme activities within each type. Proc Natl Acad Sci U S A 78(7):4226-30
22) Nordling E, et al.  (2002) Medium-chain dehydrogenases/reductases (MDR). Family characterizations including genome comparisons and active site modeling. Eur J Biochem 269(17):4267-76
23) Riveros-Rosas H, et al.  (2003) Diversity, taxonomy and evolution of medium-chain dehydrogenase/reductase superfamily. Eur J Biochem 270(16):3309-34
24) Persson B, et al.  (1999) Bioinformatics in studies of SDR and MDR enzymes. Adv Exp Med Biol 463():373-7